Glucocerebrosidase mutations in Thai patients with Parkinson's disease

Abstract

Background: GBA mutations are an important risk factor in developing Parkinson's disease (PD) worldwide. The study aimed to determine the frequency and clinical characteristics of GBA mutations in a Thai PD cohort of 480 patients and 395 control subjects.

Methods: Direct sequencing of GBA was performed in all early-onset PD patients (EOPD: n = 108) and 100 PD patients with age at onset over 50 years (AAO > 50y-PD). The study subsequently screened all identified mutations in the remaining AAO > 50y-PD patients and all control subjects. Predictive factors associated with risk of developing PD were analyzed. Comparisons of clinical characteristics of PD patients with and without GBA mutations were also carried out.

Results: Heterozygous GBA mutations were identified in 24 patients (5%) and 2 controls (0.5%). Seven identified GBA point mutations comprised p.L444P, p.N386K, p.P428S, IVS2+1G > A, IVS9+3G > C, IVS10-9_10GT > AG and c.1309delG, of which five mutations were novel. Multiple logistic regression analysis revealed that GBA mutations were more frequent in EOPD than AAO > 50y-PD groups (OR = 4.64, P < 0.022). Patients with GBA mutations had mean age at onset (43.1 ± 10.2, mean ± standard deviation) earlier than patients without GBA mutations (54.4 ± 13.9, P = 0.002). The patients with GBA mutations also had a more rapid progressive course, in which they were more likely to have higher Hoehn and Yahr staging (OR = 4.20, P = 0.006) and slightly lower means of Schwab-England ADL score [74.1 ± 17.1 vs. 81.0 ± 18.08 (OR = 0.98, 95%CI = 0.96-1.01, P = 0.162)].

Conclusion: GBA mutations are an important risk of PD in the Thai population. Patients having the mutations are likely to have early onset and may exhibit more rapid motor progression.

Keywords: Beta-glucosidase; Early-onset Parkinson's disease; Familial Parkinson's disease; Glucocerebrosidase.